The objective of the proposed research is to develop hematologically atraumatic, low prime, high capacity blood oxygenation systems for partial or total support during prolonged periods of respiratory insufficiency in pediatric and adult patients. The varied disease states indicating possible benefit from temporary, but prolonged, support with artificial lungs call for development of a variety of such units. The proposed work focuses on three aspects of membrane oxygenator systems: gas transfer-efficiency, anticoagulant therapy, and hematologic trauma. Combined studies of the three aspects are necessary for the development of physiologically compatible systems. The gas transfer studies are to include (1) mathematical and experimental analyses of gas-transfer in flowing blood, (2) development of system design theory, and (3) design of input and output systems that minimize dead-space, potted areas, and head losses. The feasibility and effectiveness of several designs for the efficient gas-transfer sections will be investigated. Among the designs to be considered are (1) non- circular straight tubes, (2) curved channels, and (3) pulsatile flow in a variety of conduits. Any proposed efficient gas-transfer design is only worthy of serious development efforts, however, if it is also shown to be hematologically atraumatic. Thrombogenesis is especially troublesome. Currently used artificial lungs require some degree of anticoagulant therapy during their use, with heparinization being the usual form. The effect of anticoagulants on hemostatic, fibrinolytic, and kallikrein systems are not fully understood and these effects become crucial during prolonged extracorporeal support. The proposed work includes long-term bypass studies of animals, with heparin or ancrod as the hemostatic anticoagulant and a variety of platelet inhibitors. The time course of multiple hematologic parameters will be evaluated using standard measurements as well as celite-activated thrombelastograms. Each animal is to serve as its own control. The efforts are expected to result in hematologic trauma evaluations of the improved membrane systems and to produce more efficient anticoagulant therapy during prolonged extracorporeal support.